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Zika spreads like wildfire, and there are more questions than answers

The Zika virus is spreading like wildfire in Brazil and other countries of South America, and is causing international alarm. The symptoms of the virus itself are usually relatively mild and it is suspicions that Zika may be causing complications after infection that are causing the most concern.

However, some specialists have cast doubt on the suspected link between Zika (ZIKV) and the birth defect microcephaly, saying there could be other reasons for the increase in microcephaly cases in northern Brazil.

It is the suspicion that Zika is causing microcephaly that prompted the World Health Organisation (WHO) to declare a global health emergency.

It is also believed that Zika may be to blame for an increase in Guillain-Barré syndrome (GBS), in which the body’s immune system attacks peripheral nerves. The syndrome can cause devastating paralysis, and can be fatal.

Colombian health officials say that three people who died after contracting GBS were infected with the Zika virus.

WHO spokesman Christian Lindmeier urges caution, however, and says the connection between Zika and GBS has not yet been proven.

The Venezuelan authorities report that three people have died from complications related to the Zika virus and officials in Brazil are investigating three deaths that they also think may be Zika-related.

There is now active local transmission of the Zika virus in 33 countries and territories, mostly in the Americas, and there are millions of reported cases.

The Zika virus has spread to 23 countries and territories in the Americas.

The Zika virus was first identified in in monkeys in Uganda in 1947, then was seen in Southeast Asia and the Pacific Islands.

The main means of Zika transmission is by the Aedes aegypti mosquito, which also spreads dengue fever and the chikungunya virus. Aedes albopictus mosquitoes may also transmit Zika.

Canada and Chile are the only countries in the Americas where the Aedes aegypti mosquito is not present.

Cases of Zika infection are also now being reported in Australia, New Zealand, Britain, and Ireland, but only in patients who had visited countries where the virus is widespread.

There are about five cases of Zika in Thailand every year, and the first 2016 case was confirmed recently. In Indonesia, 27-year-old man living in Jambi province on the island of Sumatra, who had never travelled overseas, has been found to be infected.

Brazil is the country that is being hit the hardest. The government estimates that as many as 1.5 million Brazilians may have been infected with Zika. Officials also reported an increase of nearly 50 per cent in probable cases of dengue over a three-week period in January, as compared with the same period last year.

Colombia’s national health institute says there are now more than 31,500 cases of Zika infection in the country.

More questions than answers

Only about one in five people who are infected with the Zika virus will develop symptoms. The rapid spread of a virus that has previously caused, at most, a low-grade fever, headaches, joint and muscle pain, inflamed eyes, and a rash is raising more questions than there are answers.

Is it Zika that is causing the microcephaly in newborn babies, or could a larvicide that was introduced into drinking water in northern Brazil be to blame? Why are microcephaly cases not appearing in other South American countries such as Colombia, where thousands of pregnant women have reportedly been infected with the Zika virus? Is Zika causing an increase in GBS cases? Was the spread of the virus caused by genetically modified (GM) mosquitoes released in Brazil, and would the release of more GM mosquitoes help or make matters even worse?

There are those, meanwhile, who raise the spectre of biological warfare. They are being widely dismissed as conspiracy theorists who lack proof, but the possibility that Zika was intentionally introduced cannot be dismissed.

Sexual transmission

There have been cases of Zika being spread by sexual transmission – most recently in Dallas, Texas, in the US.

The Dallas patient was infected with the virus after having sexual contact with a person who had just returned from Venezuela.

In another case, a man who travelled to Senegal in 2008 and contracted Zika is believed to have passed it on to his wife through intercourse after he returned home to Colorado. “Direct contact is implicated as the transmission route, most likely as a sexually transmitted infection,” researchers said. “Because the wife of the patient had not travelled out of the United States during the previous year and had sexual intercourse with him one day after he returned home, transmission by semen was suggested.”

In December 2013, during a Zika virus outbreak in French Polynesia, Zika was isolated from the semen of a patient in Tahiti.

“ZIKV transmission by sexual intercourse has been previously suspected,” the researchers said in a paper published in Emerging Infectious Diseases in February last year. “This observation supports the possibility that ZIKV could be transmitted sexually.”

In a more recent article in Emerging Infectious Diseases, researchers report on the case of a 68-year-old British man who became sick with the Zika virus on his return to England from the Cook Islands in French Polynesia in 2014. Traces of the virus lingered in his semen for two months, the researchers say.

“Although we did not culture infectious virus from semen, our data may indicate prolonged presence of virus in semen, which in turn could indicate a prolonged potential for sexual transmission of this flavivirus.”

There are also cases of the virus being passed on during labour and blood transfusion, which further suggests that the virus can be transmitted from person to person through bodily fluids.

Microcephaly

Brazilian officials say they suspect that Zika is the cause of an unusual number of cases of microcephaly, in which children are born with unusually small heads.

Brazil originally said it was investigating a potential link between Zika infection and more than five thousand suspected cases of microcephaly.

Of those cases, officials say 462 have been confirmed as microcephaly or other nervous system disorders and 41 have been determined to be linked to Zika.

Some scientists suggest, however, that Brazil will have fewer cases of microcephaly than originally feared, and that microcephaly cases may have been over-counted.

It has also been suggested that microcephaly cases may have been under-reported before the arrival of the virus

Colombia’s president, Juan Manuel Santos, says there is no evidence that Zika has caused any cases of microcephaly in his country, where the authorities say more than 5,000 pregnant women have been diagnosed as being infected with the virus.

Epidemiologist Christoph Zink in Berlin told CBC news in Canada that he suspects there was massive under-reporting of microcephaly in Brazil over the past five years.

Zinc suggests there could be another explanation for the recent concentration of severe microcephaly cases in the northeast. “I would ask my toxicological colleagues in Brazil to please look very closely into the practical application of agrochemicals in their country,” he told CBC.

Pediatric cardiologist Sandra Mattos says that cases of babies in Brazil with mild microcephaly date back to at least 2012, two years before the Zika virus is thought to have entered the country.

Mattos and her team carried out research in the state of Paraíba and discovered that, since 2012, a strikingly large number of babies – between 4 and 8 percent – appeared to have microcephaly, according to the broadest definitions of the term. The number of babies affected peaked in 2014, before Zika was detected in Brazil.

Doctors in Brazil were asked to report all births of babies with a head circumference of 32 centimetres or less¹; and some of those were children with normally small heads. If a baby’s head is slightly smaller than the set limit for testing, this doesn’t mean there’s neurological disease, Mattos points out.

These include the effects caused by other infections such as dengue and chikungunya; exposure to agents that can cause a birth defect, such as vaccines or drugs used in early pregnancy; and malnutrition, which has previously been associated with microcephaly and could have “an intensifying effect”. Most of the reported cases of microcephaly have occurred in low-income families, Mattos and her colleagues say.

They said the discrepancy between the “expected and found cases” may reflect a major sub-notification of microcephaly cases in recent years “coupled with an even greater epidemiological crisis than presumed, or simply the need to revise the diagnostic criteria for the condition”.

The numbers of very extreme cases of microcephaly had significantly increased in recent months, but, until recently, fell within the expected ranges for worldwide reported incidence, the researchers said.

It was possible that a high incidence of milder forms of microcephaly had been occurring well before the current outbreak, but that only extreme cases were being reported.

The researchers suggest that, as the number of extreme cases increased over the past three or four months, so did the awareness of health professionals, who started to report milder forms.

ZIKV was identified in Africa more than fifty years ago, the researchers point out, and no association with microcephaly was reported there, or in outbreaks in other parts of the world.

However, Zika had been associated with several conditions, including GBS, during a recent outbreak of the virus in French Polynesia.

Reporters for the Washington Post say some specialists are wary about the methodology used to collect data about microcephaly in Brazil. “They noted that authorities in one of the badly affected areas, the northeastern state of Bahia, have used relatively cheaper transcranial ultrasound imaging – rather than CT brain imaging scans – to try to confirm and discard cases of microcephaly.”

The more inexpensive test might not spot milder cases of the condition, pediatric neurologist and researcher at Boston Children’s Hospital, Ganeshwaran Mochida, told the Post reporters.

Suspicions about larvicide

Doctors in Argentina and Brazil have suggested that a chemical larvicide may be to blame for the cases of microcephaly in Brazil.

The Argentine doctors’ organisation, Physicians in the Crop-Sprayed Villages, has issued a report pointing to the fact that, in 2014, a chemical larvicide, Pyriproxyfen, which produces malformations in mosquitoes, was introduced into the drinking water supply in Brazil in areas where there are now the most cases of Zika.

Pyriproxyfen is used in a state-controlled programme aimed at eradicating disease-carrying mosquitoes.

Previous Zika epidemics did not cause birth defects in newborns despite infecting 75 percent of the population in the affected countries, the physicians say. Zika, they say, has traditionally been held to be a relatively benign disease.

“In other countries, such as Colombia, there are no records of microcephaly; however, there are plenty of Zika cases.”

Pyriproxyfen is manufactured by Sumitomo Chemical, a Japanese “strategic partner” of the biotech giant Monsanto. It inhibits the growth of mosquito larvae, altering the development process from larva to pupa to adult and generating malformations in developing mosquitoes, killing or incapacitating them.

The larvicide acts like a juvenile hormone, which inhibits the development of adult characteristics and reproductive development.

The physicians in Argentina stated: “Malformations detected in thousands of children from pregnant women living in areas where the Brazilian state added Pyriproxyfen to drinking water are not a coincidence, even though the ministry of health places a direct blame on the Zika virus for this damage.”

The Brazilian government, the physicians say, is trying to ignore its responsibility, “ruling out the hypothesis of direct and cumulative chemical damage caused by years of endocrine and immunological disruption of the affected population”.

The true incidence of Zika is unknown, the doctors add, “due to the fact that its clinical manifestations imitate the infection caused by the dengue virus, and to the lack of simple and reliable lab tests”.

In a separate report on the Zika outbreak and microcephaly, the Brazilian doctors’ and public health researchers’ organisation, Abrasco, also refers to the introduction of Pyriproxyfen into drinking water.

“One must question the use of chemicals on a scale that ignores the biological and environmental vulnerability of individuals and communities,” Abrasco (the Brazilian Association for Collective Health) said.

Abrasco condemns the strategy of chemical control of disease-carrying mosquitoes, which it says is contaminating people and the environment and is not reducing mosquito numbers.

Abrasco says the chemical-control strategy is a commercial manoeuvre on the part of the chemical industry, which, Abrasco says, is deeply integrated into the Latin American ministries of health, the World Health Organisation, and the Pan American Health Organisation (PAHO).

The Zika outbreak is closely linked to environmental degradation and the impacts of extractive industries, Abrasco says. The organisation cites floods caused by logging, and the massive use of herbicides on genetically modified, herbicide-tolerant soy crops.

Abrasco says the British biotech company Oxitec, which sells GM mosquitoes that are engineered for sterility, is part of the corporate lobby that is distorting the facts about Zika to suit its own profit-making agenda.

The Argentine physicians say the best defence against Zika is community-based actions. In their report, they describe the strategy of fighting disease with GM mosquitoes as “a total failure, except for the company supplying mosquitoes”.

GM mosquitoes

In a recent article in Anti-Media, Claire Bernish raises the issue of the release in Brazil of genetically modified mosquitoes (OX513A) produced by Oxitec.

The first releases took place in 2011 and 2012 in the Itaberaba suburb of the city of Juazeiro.

An initial release of 30,000 GM mosquitoes per week took place between May 19 and June 29, 2011, followed by a much larger release of 540,000 per week in early 2012, ending on February 11.

Six million GM mosquitoes were then released in the Brazilian city of Piracicaba in April 2015.

It was in May 2015 that the PAHO issued an alert about the first confirmed Zika virus infections in Brazil.

The intention of the genetic modification is to kill off the offspring when the GM males are released into the wild and mate with unaltered Aedes aegypti females.

The aim is to kill off the late larvae or pupae before they reach breeding age, but this will only work if tetracycline antibiotics are not present during the larva’s development.

The genetic engineering method employed by Oxitec allows tetracycline to be used in the lab to keep the mosquitoes alive long enough to breed. However, lethality is also reduced by the presence of antibiotics in the outside environment.

Brazil is one of the world’s biggest users of antimicrobials, including tetracycline, in its industrial farming sector.

In September 2010, molecular geneticist and developmental biologist Ricarda A. Steinbrecher (pictured left) submitted a scientific opinion to the authorities in Malaysia, where a release of Oxitec mosquitoes was being considered.

She expressed several concerns, not least the finding by Phuc et al. in 2007 that between 3 and 4 percent of first generation GM mosquitoes survive.

Her concerns were echoed by several other scientists both at the time and since then.

Steinbrecher poses a host of questions that appear not to have been investigated. “It is widely recognised that the insertion of transgenes can lead to changes that have neither been intended nor predicted and are seemingly unrelated to the nature of the gene inserted,” she said in her comments.

Claire Bernish points to an internal Oxitec document, which states that the survival rate of GM larvae could be as high as 15 percent, even with low levels of tetracycline present.

Even small amounts of tetracycline can repress the engineered lethality, Oxitec states.

“This was highlighted by a difference in results seen between our laboratory and a collaborator. They were getting 15 percent survival of a transgenic line and we were getting 3 percent! After a lot of testing and comparing experimental design, it was found that they used a cat food to feed the larvae and this cat food contained chicken. It is known that tetracycline is routinely used to prevent infections in chickens, especially in the cheap, mass-produced chicken used for animal food.

“The chicken is heat treated before being used, but this does not remove all the tetracycline. This meant that a small amount of tetracycline was being added from the food to the larvae and repressing the lethal system.”

Steinbrecher says that, even in the absence of tetracycline, a “sub-population” of genetically modified Aedes mosquitoes could theoretically develop and thrive.

Oxitec is eager to expand its operations and has regulatory approvals for import and contained testing of OX513A in Brazil, the Cayman Islands, France, India, Malaysia, Singapore, Thailand, the US, and Vietnam. In addition to the releases in Brazil, open field trials of GM mosquitoes have taken place in Grand Cayman and Malaysia.

The company says it has had huge success in decreasing the population of Aedes aegypti mosquitoes in Brazil, but the policy research and public interest group GeneWatch UK says researchers have confirmed there has been no reduction in dengue in areas where Oxitec has conducted experimental releases of GM mosquitoes.

GeneWatch UK says Oxitec has failed to conduct adequate risk assessment before releasing its GM mosquitoes into the environment.

The group lists numerous risks:

the more invasive species Aedes albopictus can move in and become the main transmitter of disease;

a reduction in the number of Aedes aegypti mosquitoes can actually increases the severity of dengue because there can be reduced human immunity to dengue haemorrhagic fever;

antibiotic resistance is spread via gut microbes in the GM mosquitoes, which are fed tetracycline; and

biting female GM mosquitoes are released and increasing numbers of GM mosquitoes survive for multiple generations because they develop resistance or encounter the antidote tetracycline in the environment.

The director of the Centers for Disease Control and Prevention in the US, Tom Frieden, pointed out on Twitter how little research has been done into Zika. Posting a photo (below) of a small sheaf of papers, he tweeted: “Entire world literature on Zika. 50 years of neglect”.

Brazil is due to host the summer Olympics from August 5 to 21. The country’s president, Dilma Rousseff, insisted yesterday that Zika would not compromise the event, but, according to the Reuters news agency, the US Olympic committee has told US sports federations that athletes and staff concerned for their health because of the virus should consider not going to the 2016 Games.

In Brazil, more than 200,000 soldiers have been deployed to visit some three million homes in a door-to-door awareness campaign.

Whatever the story behind the current outbreak of Zika, and whatever its wider implications, it is, for the people of South and Central America, a rapidly accelerating health crisis.

Aedes aegypti mosquito. Photo by Muhammad Mahdi Karim.

1) In October last year health professionals in Brazil were told to report all births of babies with a head circumference of 33 centimetres or less. After numerous false positives for microcephaly were reported, the threshold was lowered to 32 centimetres in December.

Article updated on 15/2/2016 with additional comments from doctors in Argentina, and case totals.